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Fragile X Syndrome results from a loss of Fragile X Mental Retardation Protein (FMRP). We now show that FMRP is a member of a Cav3-Kv4 ion channel complex that is known to regulate A-type potassium current in cerebellar granule cells to produce mossy fiber LTP. Mossy fiber LTP is absent in Fmr1 knockout (KO) mice but is restored by FMRP(1-297)-tat peptide. This peptide further rapidly permeates the blood-brain barrier to enter cells across the cerebellar-cortical axis that restores the balance of protein translation for at least 24 h and transiently reduces elevated levels of activity of adult Fmr1 KO mice in the Open Field Test. These data reveal that FMRP(1-297)-tat can improve function from the levels of protein translation to synaptic efficacy and behaviour in a model of Fragile X syndrome, identifying a potential therapeutic strategy for this genetic disorder.With Motor imagery (MI), movements are mentally rehearsed without overt actions; this procedure has been adopted in motor rehabilitation, primarily in brain-damaged patients. Here we rather tested the clinical potentials of MI in purely orthopaedic patients who, by definition, should maximally benefit of mental exercises because of their intact brain. To this end we studied the recovery of gait after total knee arthroplasty and evaluated whether MI combined with physiotherapy could speed up the recovery of gait and even limit the occurrence of future falls. We studied 48 patients at the beginning and by the end of the post-surgery residential rehabilitation program half of them completed a specific MI training supported by computerized visual stimulation (experimental group); the other half performed a non-motoric cognitive training (control group). All patients also had standard physiotherapy. By the end of the rehabilitation, the experimental group showed a better recovery of gait and active knee flexion-extension movements, and less pain. The number of falls or near falls after surgery was significantly lower in the experimental group. These results show that MI can improve gait abilities and limit future falls in orthopaedic patients, without collateral risks and with limited costs.Intrinsic and Te-doped GaAsSb nanowires with diameters ~100-120 nm were grown on a p-type Si(111) substrate by molecular beam epitaxy (MBE). Detailed magnetic, current/voltage and low-energy electron energy loss spectroscopy measurements were performed to investigate the effect of Te-doping. While intrinsic nanowires are diamagnetic over the temperature range 5-300 K, the Te-doped nanowires exhibit ferromagnetic behavior with the easy axis of magnetism perpendicular to the longitudinal axis of the nanowire. Sodium valproate clinical trial The temperature dependence of coercivity was analyzed and shown to be in agreement with a thermal activation model from 50-350 K but reveal more complex behavior in the low temperature regime. The EELS data show that Te doping introduced a high density of states (DOS) in the nanowire above the Fermi level in close proximity to the conduction band. The plausible origin of ferromagnetism in these Te-doped GaAsSb nanowires is discussed on the basis of d0 ferromagnetism, spin ordering of the Te dopants and the surface-state-induced magnetic ordering.The discovery of borospherenes unveiled the capacity of boron to form fullerene-like cage structures. While fullerenes are known to entrap metal atoms to form endohedral metallofullerenes, few metal atoms have been observed to be part of the fullerene cages. Here we report the observation of a class of remarkable metallo-borospherenes, where metal atoms are integral parts of the cage surface. We have produced La3B18- and Tb3B18- and probed their structures and bonding using photoelectron spectroscopy and theoretical calculations. Global minimum searches revealed that the most stable structures of Ln3B18- are hollow cages with D3h symmetry. The B18-framework in the Ln3B18- cages can be viewed as consisting of two triangular B6 motifs connected by three B2 units, forming three shared B10 rings which are coordinated to the three Ln atoms on the cage surface. These metallo-borospherenes represent a new class of unusual geometry that has not been observed in chemistry heretofore.The original version of this article contained an error in the spelling of the author Yuchen Chen, which was incorrectly given as Yuhuan Chen. This has now been corrected in both the PDF and HTML versions of the article.Large-scale changes in global climate at the end of the Pleistocene significantly impacted ecosystems across North America. However, the pace and scale of biotic turnover in response to both the Younger Dryas cold period and subsequent Holocene rapid warming have been challenging to assess because of the scarcity of well dated fossil and pollen records that covers this period. Here we present an ancient DNA record from Hall's Cave, Texas, that documents 100 vertebrate and 45 plant taxa from bulk fossils and sediment. link2 We show that local plant and animal diversity dropped markedly during Younger Dryas cooling, but while plant diversity recovered in the early Holocene, animal diversity did not. Instead, five extant and nine extinct large bodied animals disappeared from the region at the end of the Pleistocene. Our findings suggest that climate change affected the local ecosystem in Texas over the Pleistocene-Holocene boundary, but climate change on its own may not explain the disappearance of the megafauna at the end of the Pleistocene.Recent progress in high power ultrafast short-wave and mid-wave infrared lasers has enabled gas-phase high harmonic generation (HHG) in the water window and beyond, as well as the demonstration of HHG in condensed matter. In this Perspective, we discuss the recent advancements and future trends in generating and characterizing soft X-ray pulses from gas-phase HHG and extreme ultraviolet (XUV) pulses from solid-state HHG. Then, we discuss their current and potential usage in time-resolved study of electron and nuclear dynamics in atomic, molecular and condensed matters.The endothelial lipase LIPG possesses serine phospholipase activity and is involved in lipoprotein metabolism. Our previous studies have revealed that LIPG overexpression is required for tumor formation and metastasis of human basal-like triple-negative breast cancer (TNBC). We also demonstrated that LIPG differentially regulates TNBC malignancy through its enzymatic and non-enzymatic functions. The present studies were aimed at determining how XEN445, a specific inhibitor targeting LIPG phospholipase activity, impacts on TNBC tumor formation and malignant features. We established a cell-based LIPG enzymatic assay system to measure the inhibitory effect of XEN445 on LIPG phospholipase activity and determine its IC50. We found that XEN445 preferentially inhibited the proliferation of LIPG-expressing TNBC cells but not LIPG-negative luminal breast cancer cells. XEN445 inhibited the self-renewal of cancer stem cells (CSCs) in vitro and TNBC tumor formation in vivo. However, XEN445 had no inhibitory effect on the invasiveness and CSC stemness of TNBC cells. Our studies suggest that targeting both LIPG enzymatic and non-enzymatic functions is an important strategy for the treatment of TNBC.Trifluoroethanol and difluoroethanol units are important motifs in bioactive molecules, but the methods to direct incorporate these units are limited. Herein, we report two organosilicon reagents for the transfer of trifluoroethanol and difluoroethanol units into molecules. Through intramolecular C-Si bond activation by alkoxyl radicals, these reagents were applied in allylation, alkylation and alkenylation reactions, enabling efficient synthesis of various tri(di)fluoromethyl group substituted alcohols. The broad applicability and general utility of the approach are highlighted by late-stage introduction of these fluoroalkyl groups to complex molecules, and the synthesis of antitumor agent Z and its difluoromethyl analog Z'.Forestland soils play vital role in regulating global soil greenhouse gas (GHG) budgets, but the interactive effect of the litter layer management and simulated nitrogen (N) deposition on these GHG flux has not been elucidated clearly in subtropical forestland. link3 A field trial was conducted to study these effects by using litter removal method under 0 and 40 kg N ha-1 yr-1 addition in a subtropical forestland in Yingtan, Jiangxi Province, China. Soil CO2 emission was increased by N addition (18-24%) but decreased by litter removal (24-32%). Litter removal significantly (P less then 0.05) decreased cumulative N2O emission by 21% in treatments without N addition but only by 10% in treatments with 40 kg N ha-1 yr-1 addition. Moreover, litter-induced N2O emission under elevated N deposition (0.094 kg N2O-N ha-1) was almost the same as without N addition (0.088 kg N2O-N ha-1). Diffusion of atmospheric CH4 into soil was facilitated by litter removal, which increased CH4 uptake by 55%. Given that the increasing trend of atmospheric N deposition in future, which would reduce litterfall in subtropical N-rich forest, the effect of surface litter layer change on soil GHG emissions should be considered in assessing forest GHG budgets and future climate scenario modeling.Currently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation. We show that exon skipping enabled trimer formation, leading to remarkable clinical and pathological improvements including expression of the α5 chain on glomerular and the tubular basement membrane. In addition, the survival period was clearly prolonged in the ASO treated mice group. This data suggests that exon skipping may represent a promising therapeutic approach for treating severe male XLAS cases.Ensuring lumpfish health and welfare in salmon farms is vital to reduce the high mortality rates reported and to guarantee a high delousing efficiency. Recent observations of farmed lumpfish livers have shown colours ranging from pale (colours 1 and 2), through bright orange (colours 3 and 4), to dark reddish-brown (colours 5 and 6), some of which may be related to welfare condition. To characterize the status of lumpfish deployed in four Faroese salmon farms, several welfare indicators were assessed a weight-length relationship, scoring of external physical damage, and after dissection, stomach content and liver colour scoring. Liver samples were weighed, stored and analysed for lipid content, lipid classes, total pigments, fatty acid profile and histopathology to explain the differences between the mentioned liver colours. Bright orange livers, liver colours 3 and 4, were related to increased levels of carotenoid pigments rather than levels of lipids and appear to reflect good fish welfare. However, dark reddish-brown colours, liver colours 5 and 6, were associated with very low levels of triacyl glycerides in the liver, indicating use of lipid reserves and poor welfare condition. Histopathology confirmed that the dark reddish-brown livers, liver colours 5 and 6, formed a distinct group. Thus, liver colour was shown to be a good welfare indicator and should be monitored in farms.
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